Neild G H, Rocchi G, Imberti L, Fumagalli F, Brown Z, Remuzzi G, Williams D G
Thromb Res. 1983 Nov 15;32(4):373-9. doi: 10.1016/0049-3848(83)90090-7.
NZW rabbits with acute serum sickness given Cyclosporin A (CyA) 25 mg/kg/day develop glomerular capillary thrombosis similar to that seem in the haemolytic uraemic syndrome (HUS). Bone marrow recipients treated with CyA may also develop a similar renal lesion associated with a haemolytic uraemic-like syndrome. In the HUS, impaired production of prostacyclin by vascular tissue may be found and has been associated with a lack of a plasma factor which stimulates prostacyclin synthesis. We therefore examined, in six normal rabbits, treated with CyA 25 mg/kg for five days, the ability of plasma from treated and untreated rabbits to stimulate prostacyclin synthesis from normal rabbit aortic rings. Plasma from untreated rabbits produced 21.5 +/- 6.9 ng 6-keto PGF1 alpha/ml/mg wet weight aorta (mean +/- SEM). However, the ability of plasma from CyA-treated rabbits to stimulate prostacyclin production was profoundly reduced. This was apparent within 24 hours of starting and persisted for seven days after therapy was stopped: mean of values from all rabbits bled from start of therapy until seven days after therapy stopped was 3.7 +/- 0.5 ng/ml/mg. We suggest that the renal complications of CyA therapy are related to a failure of normal vascular prostacyclin synthesis due to lack of a prostacyclin-stimulating plasma factor.
给予环孢素A（CyA）25mg/kg/天的急性血清病新西兰白兔会出现类似于溶血性尿毒症综合征（HUS）中所见的肾小球毛细血管血栓形成。接受CyA治疗的骨髓移植受者也可能出现与溶血性尿毒症样综合征相关的类似肾脏病变。在HUS中，可能会发现血管组织中前列环素生成受损，这与缺乏刺激前列环素合成的血浆因子有关。因此，我们对6只正常兔子进行了研究，用25mg/kg的CyA治疗5天，观察经治疗和未经治疗兔子的血浆刺激正常兔主动脉环合成前列环素的能力。未经治疗兔子的血浆产生21.5±6.9ng 6-酮-前列腺素F1α/毫升/毫克湿重主动脉（平均值±标准误）。然而，经CyA治疗兔子的血浆刺激前列环素产生的能力显著降低。这在开始治疗后24小时内就很明显，并在停止治疗后持续7天：从治疗开始到治疗停止后7天内所有兔子采血所得值的平均值为3.7±0.5ng/毫升/毫克。我们认为，CyA治疗的肾脏并发症与由于缺乏刺激前列环素的血浆因子而导致正常血管前列环素合成失败有关。
